The cardiotoxic effects of anthracyclines are well documented, and a growing body of experimental evidence has implicated reactive forms of oxygen in this life-threatening toxicity. Adriamycin and other anthracycline anticancer drugs can be enzymatically activated to semiquinone free radical intermediates which auto-oxidize to generate superoxide anion radical and other highly reactive and toxic oxygen species such as hydrogen peroxide, hydroxyl radical and singlet oxygen. These oxyradicals and activated species of oxygen can cause toxicity by attacking and damaging intracellular target molecules including nucleic acids, structural proteins, enzymes and, especially, membrane unsaturated lipids. Reactive oxygen attack of membrane lipids causes extensive damage by the process of membrane lipid peroxidation, which not only disrupts the structural integrity of the membrane, but also inactivates membrane bound enzymes and produces toxin, reactive aldehyde products which can alkylate proteins and nucleic acids. Thus, anthracycline-enhanced membrane lipid peroxidation may cause damage by both direct and by secondary mechanisms. The present projects were designed to evaluate this hypothesis and to better understand the possible biochemical and molecular mechanisms which contribute to anthracycline cardiac toxicity.